Conventional cancer imaging is inaccurate and imprecise. Typically a patient has a marker, or other chemical compound, injected into their circulatory system, waits about 1 hour and is then imaged using Positron Emission Tomography (PET). The 1 hour time frame is quite short and may not be representative of the general activity of the entire number of cancer cells.
The reason why conventional cancer imaging is inaccurate and imprecise is because, in part, the metabolic uptake of an imaging marker has a cell cycle-specific mechanism of action. More specifically, uptake of the imaging marker is a function of which part of the cycle targeted cell are in. During any given hour, which is the typical wait time between marker administration and imaging, the cancer cells to be imaged may be at any stage of the cell cycle and may uptake and absorb the marker at different rates and amounts. This variance, which exists between all of the cancer cells throughout the patient, can cause misleading results and improper diagnoses.
The cell cycle is the series of events occurring in a cell leading to its division and duplication. In eukaryotic cells, the cycle can be divided into two periods, interphase and mitosis. Transit through these two periods of the cell cycle is known as proliferation. During interphase, the cell grows, accumulates nutrients needed for mitosis and duplicates its DNA. During mitosis, the cell splits itself into two distinct daughter cells. Interphase includes three distinct phases, Gap 1 (G1) phase, S phase and Gap 2 (G2) phase while mitosis includes two processes. G1 phase includes the cell increasing in size, biosynthetic activities of the cell increasing and the synthesis of enzymes needed for DNA replication in the subsequent step. S phase includes the beginning of DNA synthesis and replication of all of the chromosomes. G2 phase lasts until the cell enters mitosis and includes protein synthesis including the production of microtubules for mitosis. Mitosis includes a process where the cell's chromosomes are divided between the two daughter cells and a cytokinesis process where the original cell's cytoplasm divides forming two distinct daughter cells. The cell cycle also includes a resting phase, typically referred to as G0. The boundaries between the various phases, for example the boundary between the G1 and S phase is referred to as a cell cycle checkpoint.
The progression of the cell cycle can be inhibited, so that a particular cell stops the cycle at a point, a cellular checkpoint, before proceeding to the next phase. Cell cycle checkpoints are located between the different phases of the cell cycle, with two of the checkpoints being at the interface between the G1 and the S phase (G1/S) and the interface between the G2 and M phase. A cell cycle inhibitor can stop the progression of a cell from passing to the next phase, for example a cell can be inhibited at the G1/S cell cycle checkpoint, which forces the cell to remain in the G1 phase until the inhibitor is removed.
In any particular cancer cell population or tumor in an individual, the length of the cell cycle is variable. This variability is due to differing periods spent in G1 of G0 while the length of time from the beginning of S phase to the end of M phase is relatively constant.
Imaging using traditional markers relies on the increased uptake of the marker because of the increased metabolic activity of the cancer cells. This increased uptake is most noticeable once the cancer cells are in the S phase as opposed to the other cell cycle stages. If the majority of cancer cells to be imaged are not in the S phase during the typically one hour time span between administration and imaging, the image result may not be representative of the actual concentration and location of cancer cells.
What is desired is a treatment to arrest the cell cycle for a clinically relevant fraction of cells at the G1/S cell cycle checkpoint, so that the efficacy of imaging markers can be enhanced.